Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of proteolytic enzymes such as cathepsin and elastase in platelets and the important role of collagen in platelet aggregation suggested that collagenase might be present in platelets. Epinephrine, ADP, and collagen liberate collagenase from platelets in plasma as measured by the hydrolysis of [(14)C]glycine-labeled collagen fibrils. The collagenase activity appeared in an early phase of platelet aggregation and was not a part of the release reaction. However, only 50% of the total collagenase could be liberated by the aggregating agents used. Sucrose density gradient analysis of platelet homogenates using appropriate sub-cellular markers indicated that collagenase appeared in both the granule and membrane fractions. Gel-filtered platelets failed to show collagenase activity before exposure to aggregating agents but released more collagenolytic activity than was found in platelet-rich plasma. This observation was explained by the finding that collagenolytic activity was inhibited by normal human plasma. One of the inhibitors is alpha(1)-antitrypsin as demonstrated by decreased inhibition in plasma from a patient with homozygous alpha(1)-antitrypsin deficiency. Platelet collagenase activity could also be demonstrated by its ability to decrease the viscosity of collagen solutions and to produce collagen fragments similar to those produced by other mammalian collagenases on disk gel electrophoresis. The observation that partially purified platelet collagenase could destroy the platelet-aggregating activity of collagen suggests that the enzyme might function in a negative feedback mechanism limiting thrombus formation.
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PMID:Human platelet collagenase. 436 8

1. An enzyme present in rat liver extracts degraded insoluble collagen maximally at pH3.5. Collagenolytic activity was more abundant in kidney, spleen and bone marrow and was also present in decreasing concentrations in ileum, lung, heart, skin and muscle. 2. The crude collagenolytic cathepsin was activated by cysteine and dithiothreitol, but not by 2-mercaptoethanol. Iodoacetamide, p-chloromercuribenzoate and 7-amino-1-chloro-3-l-tosylamidoheptan-2-one hydrochloride inhibited the enzyme. Zn(2+), Fe(3+) and Hg(2+) ions were strongly inhibitory, but Ca(2+), Co(2+), Mg(2+) and Fe(2+) ions had little or no effect. EDTA was an activator of the enzyme. Inhibitors of cathepsin B were found to enhance collagenolysis, but phenylpyruvic acid, a cathepsin D inhibitor, inhibited the enzyme. Di-isopropyl phosphorofluoridate had no effect. 3. Collagenolysis at pH3.5 and 28 degrees C was restricted to cleavage of the telopeptide region in insoluble collagen, and the material that was solubilized consisted mostly of alpha-chains. 4. The collagenolytic cathepsin was separated from cathepsins B2 and D by fractionation on Sephadex G-100 and a partial separation from cathepsin B1 was obtained by chromatography on DEAE-Sephadex. 5. The function of the collagenolytic cathepsin in the catabolism of collagen is discussed in relation to the action of the other lysosomal proteinases and the neutral collagenase.
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PMID:The nature of the collagenolytic cathepsin of rat liver and its distribution in other rat tissues. 465 Nov 35

Changes in collagen fractions as well as in the activity of leucocytic collagenase and collagenolytic cathepsin of rats after 30 days of gamma-rays exposure were examined. A statistically significant decrease in total collagen content resulting from the reduction of salt--soluble (NSC) and acid--soluble (ASC) collagen fractions was found. An increased content of insoluble collagen fraction (ISC) may confirm the opinion about stimulative gamma-rays influence upon cross--links formation. An increase in collagenolytic enzymes activity may account for an elevated degradation of collagen; with a contribution of leucocytic collagenase and collagenolytic cathepsin. Perhaps the quantitative increase in insoluble collagen stimulates elevated biosynthesis of collagenolytic enzymes determining the process of protein degradation. Further investigations are needed to explain the radiobiological effects of gamma-rays on the connective tissue.
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PMID:[Effects of ionizing radiation on the content of total collagen and its fractions and the activity of collagenolytic enzymes in rat tissues]. 628 19

Whole isolated rat glomeruli (WG) were incubated with bacterial collagenase to separate epithelial cells (EC) from the cores of glomerular tufts (GC), which consisted of mesangial and endothelial cells, as demonstrated by electron microscopy. Lysates of WG, EC, and GC and of renal tubules were prepared by hypo-osmotic shock and freeze-thawing. Activities of the following acidic lysosomal hydrolases were measured: acid phosphatase, beta-glucuronidase, cathepsin-D, non-specific esterase, and aryl sulfatases A and B. The glomerular cell preparations showed activities of all studied enzymes. GC had higher activities than EC, save for nonspecific esterase. Studies of the recovery of acid phosphatase and beta-glucuronidase revealed that approximately 2/3 of the hydrolase activities present in WG was still measureable after collagenase treatment and that the bulk of this was found in the GC lysates. These findings demonstrate that the rat glomerulus and its cell components have considerable biochemical activities of acidic hydrolytic enzymes. These appear to be most prominent in the combined mesangial and endothelial cells of the GC components.
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PMID:Lysosomal enzymes in glomerular cells of the rat. 628 26

Cardiomyopathy was produced by isoprenaline injections to healthy and hydrazinophthalazine-treated rats. The activity of leukocyte collagenase and collagenolytic cathepsin was determined on the 2nd, 7th, 19th and 21st day after the last isoprenaline injection. At the same time morphological studies of the heart muscles were carried out. It was found that alterations in enzyme activity were different in healthy and hydrazinophthalazine-treated rats. A negative synergism of isoprenaline as regards the hydrazinophthalazine action was observed in biochemical and morphological studies.
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PMID:Leukocyte collagenolytic activity in normal and hydrazinophthalazine-treated rats during isoprenaline-induced cardiomyopathy. 630 34

Proteolytic and sialyltransferase activities were determined in extracts of 65 human primary breast tumors, 6 lymph node metastases, 6 fibroadenomas and 27 normal tissues. Using proteins and synthetic selective substrates, we observed the presence of collagen-peptidases, plasminogen activator, cathepsin-B and cathepsin-D-like enzymes, and sialyltransferase. No active or trypsin-activatable type-IV collagenase activity was detected. Although individual variations between tumors were large, proteinase and sialyltransferase contents were significantly elevated in malignant breast tissues. Enzyme activities were found to be related to the epithelial volume of the tumor. No significant correlation was found between the proteinase or sialyltransferase activities and the degree of differentiation of the tumor cells, or the degree to which tumors had metastasized to regional lymph nodes. Since large variations of enzyme levels apparently reflect the heterogeneity of epithelial cell densities in tumor samples, proteolytic or sialyltransferase activities cannot therefore be used as a measure of quantitative evaluation of invasive properties in breast cancer.
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PMID:Proteinases and sialyltransferase in human breast tumors. 632 71

Collagen metabolism was studied in patients with viral hepatitis, chronic hepatic disorders as well as under experimental conditions, in rats with carbon tetrachloride-induced hepatic fibrosis. Changes in serum hydroxyproline, hydroxylysine and collagen-like protein levels, and collagen peptidase activity were observed in clinical investigations. An increase of collagen content and collagen-glycosaminoglycan interactions were found in the liver samples of rats with the hepatic fibrosis. An increase of collagenase activity in the course of fibrosis is due to an elevated biosynthesis of the enzyme de novo as well as to a decreased content of inhibitors. The activity of collagen peptidase and collagenolytic cathepsin were increased, and it was suggested that an increase of collagen degradation in the liver was a self-defensive mechanism against fibrosis but insufficient to protect the organ against it. This was caused probably by changes in susceptibility of collagen to degradating enzymes in the course of chronic hepatic disorders.
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PMID:Clinical and experimental studies on collagen metabolism in hepatic disorders. 633 Aug 69

Graded compensatory renal growth was induced either by unilateral (UNX) or 5/6 nephrectomy (5/6-NX). Over the experimental period of 16 weeks, kidney weight increased by 59% in SHAM animals, while the remaining kidney in UNX rats more than doubled its initial weight. The hypertrophic response was most pronounced in the remnant kidney after 5/6-NX with a four fold increment in kidney weight. Morphologically glomerular volume increased moderately after UNX (+27%), while 5/6-NX was associated with marked glomerular hypertrophy (+87%). Significant focal sclerosis was found in 11% of glomeruli in the remaining kidney after UNX. By contrast 83% of glomeruli wre sclerosed in the remnant kidney after 5/6-NX. In parallel, there was a significant increase in the glomerular protein/DNA ratio (+23%) in 5/6-NX but not in UNX animals. These glomerular alterations were associated with lower glomerular cysteine and metalloproteinase activities (collagenase, -57%; gelatinase, -49%) in 5/6-NX rats, while UNX rats had normal glomerular proteinase activities. In terms of tubular proteinases, cathepsin activities were significantly lower in UNX rats (cath. L+B, -38%; cath. B, -37%; cath. H, -27%) and more so after 5/6-nephrectomy (cath. L+B, -72%; cath. B, -73%; cath. H, -73%), while metalloproteinase activities were only reduced in 5/6-NX rats (collagenase, -35%; gelatinase, -58%). These findings demonstrate that kidney hypertrophy is associated with reduction in renal proteinase activities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of proteinases in renal hypertrophy and matrix accumulation. 756 7

The tissue localization and content of the proteolytic enzyme cathepsin G and its inhibitor alpha 1-antichymotrypsin were studied in the local host reaction to loosening of total hip-replacement prostheses in eleven patients and were compared with those in samples of non-inflammatory tissue from the synovial capsule obtained during arthroscopies of the knee. Immunostaining demonstrated cellular localization of cathepsin G in 71 per cent of monocyte or macrophage-like cells and in 46 per cent of fibroblast-like cells in the samples of interface tissue between the bone and the loose acetabular component obtained at the time of the total hip replacements, and in 59 and 42 per cent, respectively, in the samples of pseudocapsular tissue obtained at the same time, whereas the synovial lining cells in the samples of non-inflammatory tissue from the synovial capsule revealed only a slight immunoreactivity to cathepsin G. Cathepsin-G activity was also measured with synthetic succinyl-alanine-alanine-proline-phenylalanine-paranitroanilide as a substrate, the degradation of which was monitored spectrophotometrically. In accordance with results from immunohistochemical studies, cathepsin-G activity was found in the samples of interface tissue (31.6 international units per liter) and the samples of pseudocapsular tissue (15.5 international units per liter) obtained during the total hip replacements, whereas the level of cathepsin-G was low in the samples of non-inflammatory synovial capsular tissue (2.5 international units per liter). Cathepsin-G activity in the samples of pseudosynovial fluid obtained at the time of the total hip replacements was low (2.4 international units per liter), although immunoblot analysis showed marked immunoreactive cathepsin G in the samples of pseudosynovial fluid. This low activity of cathepsin G might be explained by the presence of alpha 1-antichymotrypsin, which was detected by laser nephlometric immunoassay and immunoblot analysis. These results demonstrate increased concentration of cathepsin G locally in the tissues around loose total hip-replacement prostheses. Because cathepsin G is not only able to act on extracellular matrix components (such as gelatin, proteoglycan, elastin, and laminin) at a physiological pH but also is able to activate collagenase, gelatinase, and stromelysin proenzymes, to inactivate tissue inhibitor of metalloproteinases, and to modulate tumor necrosis factor-alpha, it may play an important role in the degradation of periprosthetic connective tissue and in the lysis of bone around the implant, thus contributing to the loosening of prostheses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cathepsin G and alpha 1-antichymotrypsin in the local host reaction to loosening of total hip prostheses. 782 51

The presence and activity of proteolytic enzymes has been investigated in vitro on soluble and insoluble preparations obtained from both unimplanted and implanted glutaraldehyde-treated bovine parietal pericardium. Using detection by colorimetric techniques, soluble preparations were shown to hydrolyze enzyme substrates that are characteristic for trypsin-like proteases, cathepsin-like proteases, and collagenase. As detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in gradient gels and gel filtration on Sepharose CL-6B, insoluble (pellet) preparations degraded denatured type I collagen in a time-dependent pattern, producing low-molecular-weight fragments. These activities were partially inhibited by phenylmethylsulfonyl fluoride, N-ethyl maleimide, soybean trypsin inhibitor, para-chloromercuribenzoic acid, or ethylenediaminetetraacetic acid, suggesting the presence of a heterogeneous enzymatic mixture. Insoluble preparations incubated with pure pericardial dermatan sulfate proteoglycan detached the glycosaminoglycan chains from their core protein carrier, producing a digestion pattern similar to Cathepsin C. These findings demonstrate the presence of active proteases in glutaraldehyde-fixed bovine pericardium per se and in explanted pericardial bioprosthetic cardiac valves, an additional factor that might contribute to intrinsic extracellular matrix degeneration in pericardial bioprosthetic devices.
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PMID:Detection of remnant proteolytic activities in unimplanted glutaraldehyde-treated bovine pericardium and explanted cardiac bioprostheses. 840 12


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